In order to study the functional role of substance P in substantia nigra, we have studied the interaction between substance P and dopamine neurons. Chronic treatment of rats with haloperidol resulted in a significant decrease of substance P concentration in substantia nigra; in contrast, that of other regions such as striatum and hypothalamus was not affected. This finding suggests that a dopamine neuron may be involved in regulating substance P content in the substantia nigra. A decrease in the substance P concentration occurred only after chronic treatment, and not after acute injection of the drug, indicating that a large pool of substance P precursor may exist. We will use the chick embryo dorsal root ganglion to study whether a precursor(s) is involved in the formation of substance P.